Functional proteomics reveals the protective effects of saffron ethanolic extract on hepatic ischemia-reperfusion injury
Functional proteomics reveals the protective effects of saffron ethanolic extract on hepatic ischemia-reperfusion injury
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DOI：
10.1002/pmic.201200551
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发表时间：
2013-08-01
期刊：
影响因子：
3.4
通讯作者：
Wu, Yang-Chang
中科院分区：
文献类型：
--
作者：
Pan, Tai-Long;Wu, Tung-Ho;Wu, Yang-Chang
肝脏缺血再灌注（IR）损伤是一个常见的临床问题，ROS可能是IR损伤的一个促成因素。目前的研究评估了藏红花乙醇提取物 (SEE) 在大鼠模型中对肝 IR 损伤的潜在保护作用。 Caspases 3 和末端脱氧核苷酸转移酶介导的 dUTP 生物素缺口末端标记 (TUNEL) 结果显示 IR 样品中细胞死亡增加；相反，SEE/IR 组中检测到轻微的细胞凋亡。 SEE预处理显着恢复了抗氧化酶（SOD1和过氧化氢酶）的含量，并在减少p47phox易位方面显着抑制了细胞内ROS浓度。蛋白质组工具显示，IR 组和 SEE/IR 组之间有 20 种蛋白质的蛋白质强度受到显着调节。特别是，SEE 给药可以减弱几种伴侣蛋白的羰基化水平。网络分析表明，藏红花提取物可以缓解红外线诱导的内质网应激和蛋白质泛素化，最终导致细胞凋亡。总而言之，SEE 可以通过调节蛋白质氧化来减少肝脏 IR 损伤，我们的结果可能有助于开发针对 ROS 引起的疾病的新治疗策略。
Hepatic ischemia-reperfusion (IR) injury is a common clinical problem and ROS may be a contributing factor on IR injury. The current study evaluates the potential protective effect of saffron ethanol extract (SEE) in a rat model upon hepatic IR injury. Caspases 3 and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) results showed increased cell death in the IR samples; reversely, minor apoptosis was detected in the SEE/IR group. Pretreatment with SEE significantly restored the content of antioxidant enzymes (SOD1 and catalase) and remarkably inhibited the intracellular ROS concentration in terms of reducing p47phox translocation. Proteome tools revealed that 20 proteins were significantly modulated in protein intensity between IR and SEE/IR groups. Particularly, SEE administration could attenuate the carbonylation level of several chaperone proteins. Network analysis suggested that saffron extract could alleviate IR-induced ER stress and protein ubiquitination, which finally lead to cell apoptosis. Taken together, SEE could reduce hepatic IR injury through modulating protein oxidation and our results might help to develop novel therapeutic strategies against ROS-caused diseases.